Pregnenolone sulphate improves memory processing in early-handled female rats

Early life experiences lead to sex-specific behavioural and neurochemical changes in adulthood. Indeed, early handling enhances learning and memory in male rats (Cannizzaro et al., 2005), whereas it impairs learning performance in female adult rats, a finding that has been correlated to decreased nitric oxide (NO) production in the hippocampus (Noschang et al., 2010). Pregnenolone sulfate (PREGS) is considered as one of the most potent memory-enhancing neurosteroids, since its activity as a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs) (Vallée et al., 2001). Given these premises, this study a…

Chronic prenatal treatment with 5-methoxytryptamine reduced depressive-like behaviour induced by forced swim test in mature male rats

Exposure to ototoxic agents and hearing loss: A review of current knowledge

Several experimental and clinical studies have shown that a variety of ototoxic agents (such as drugs, industrial chemicals and noise) can cause sensorineural hearing loss. The most common ototoxic drugs used in clinical practice include: aminoglycoside and macrolide antibiotics, quinoline anti-malarials, platinum analog antineoplastics, loop diuretics, and acetylsalicylic acid. Among chemical agents with potential ototoxic properties are: organic solvents, heavy metals, organotins, nitriles, asphyxiants, and pesticides/herbicides. Acoustic exposure to high intensity and/or prolonged noise can also cause permanent threshold shifts in auditory perception. Ototoxic agents can influence audito…

Locomotor and antidepressant-like effects of 5-HT(1A) agonist LY 228729 in prenatally benzodiazepine-exposed rats.

Locomotor activity and antidepressant-like effect in the forced swim test (FST) of 5-HT(1A) agonist LY 228729 were investigated in adult rats prenatally exposed at doses of diazepam (DZ) and alprazolam (ALP) which induce persistent downregulation of GABA/ benzodiazepine (BZ) receptors. Prenatal exposure to ALP and DZ did not modify the efficacy of subchronic LY 228729 to decrease immobility time in the FST. Prenatal DZ and ALP potentiated the facilitatory effect of subchronic LY 228729 on locomotor activity; prenatal DZ was more effective than prenatal ALP. Moreover, prenatal DZ increased stereotypic movements induced by LY 228729. These data suggest that the persistent downregulation of GA…

Ethanol stimulates corticotropic releasing hormone (CRH) release from rat hypothalamic explants; role of acetaldehyde

Ethanol is able to activate the hypothalamic-pituitary-adrenal (HPA) axis, and to modify its response to other stressors, releasing adrenocorticotropic hormone (ACTH), and glucocorticoid release, (Lee et al 1999, 2000). In the brain ethanol is diverted by catalase activity into acetaldehyde, which is reported to mediate some of its behavioural and neurochemical effects. (Peana et al 2008, Melis et al 2007) Thus, to clarifìy the mechanisms underlying ethanol activity on the HPA axis we investigated :1) ethanol effect on CRH release from incubated hypothalamic explants; 2) the role of acetaldehyde (ACD), in mediating ethanol activity. To this aim, rat hypothalamic explants were incubated with…

Alcohol preference, behavioural reactivity and cognitive functioning in female rats exposed to a three-bottle choice paradigm.

Alcohol abuse is a substantial and growing health problem in Western societies. In the last years in vivo and in vitro studies have suggested that males and females display a different alcohol drinking behaviour, with swingeing differences not only in the propensity for alcohol use but also in the metabolic and behavioural consequences. In this study we investigated, in adult female rats, ethanol self-administration and preference pattern using a 3-bottle paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on explorative behaviour in the open field (OF), and on spatial learning and reference memory in the Morri…

Antidepressant and anxiolytic effects of alprazolam versus the conventional. antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats

The antidepressant and anxiolytic effects of alprazolam were compared to those of desipramine, diazepam and buspirone in the forced swim test. Subchronic alprazolam induced a reduction in immobility similar to that of desipramine in 'non-pretested' and 'pretested' rats. In 'non-pretested' rats, the anti-immobility effect of desipramine was potentiated by diazepam and alprazolam, given before subchronic desipramine, while the anti-immobility effect of subchronic alprazolam was counteracted by diazepam. Diazepam, administered before the pretest session, counteracted, 24 h later, the anti-immobility effect of subchronic desipramine and alprazolam; alprazolam counteracted the anti-immobility ef…

Effects of pre- and postnatal exposure to 5-methoxytryptamine and early handling on an object-place association learning task in adolescent rat offspring.

A reduction in 5-HT1A receptor response enhances learning and memory performance in rats. Pre- and postnatal treatment with 5-methoxytryptamine (5MT), a non-selective serotonergic agonist, and early handling, reduce the number of 5-HT1A receptors in neonatal and pre-pubertal rat progeny. The aim of this study was to investigate in adolescent male rats the consequences of pre- and postnatal treatment with 5MT and its interaction with early handling on an object-place association learning task, the "Can test", a motivated, non-aversive, spatial/object discrimination task. Results show that a single daily injection of 5MT from gestational days 12 to 21 (1 mg/kg s.c.) and from postnatal days 2 …

Long-lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam

Environmental stressors can substantially affect the adaptive response of rats to novelty in a sexually dimorphic manner. Gender-related differences are also observed in neurochemical and behavioural patterns of adult rats following prenatal exposure to diazepam (DZ). In the present study the behavioural reactivity to novelty is investigated in open field (OF) and in acoustic startle reflex (ASR) tests, in non handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male and female rats prenatally exposed to DZ. A single daily s.c. injection of DZ (1.5 mg/kg) over gestation days 14-20 decreases GABA/BDZ receptor function in both sexes, as shown by the decreased electro…

Presynaptic effects of anandamide and WIN55,12-2 on glutamergic nerve endings isolated from rat hippocampus

Role of acetaldehyde in alcohol addiction: current evidence and future perspectives

The effects of alcohol have been widely studied during the past century, corroborating the idea that this tiny chemical compound acts throughout most of our neurotransmitter systems since it is capable of inducing addictive behaviour. Two of the most serious problems of alcohol addiction are craving and relapse; several studies have demonstrated that relapse is related to the anxious state which occurs during withdrawal, and it has been proved that this behavioural modifications results from an alteration of the dopaminergic and serotonergic systems. An important role in the neurobiology of alcohol addiction is played by acetaldehyde (ACD), ethanol first metabolite. Our recent studies indee…

Role of CB2 receptors and cGMP pathway on the cannabinoid-dependent antiepileptic effects in an in vivo model of partial epilepsy.

This study aimed at providing an insight on the possible role of cannabi-noid (CB) type 2 receptors (CB2R) and cGMP pathway in the antiepileptic activity ofWIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone, a non-selective CB agonist, in the maximal dentate activation (MDA) model of partial epilepsy in adult male rats. We evaluated the activity of a CB2 antagonist/inverse agonist AM630, [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone or 6-iodopravadoline, alone or in co-administration with WIN 55,212-2. Also, in the MDA model it was investigated the co-treatment of WIN55,212…

Manipulations of glucocorticoids induced stress response may differently affect the acquisition of a reward-facilitated spatially/visual learning task.

Behavioural and pharmacological characterization of a novel cannabimimetic adamantane-derived indole, APICA, in C57BL/6J mice

The novel adamantane derivative APICA (N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabimimetic indole of abuse (1, 2). Despite its novel structure, APICA recalls cannabimimetic indoles, such as representative member JWH-018. The emerging abuse problem, together with the paucity of information about the bioactivity of APICA (3) emphasize the need for further evaluation of the in vivo pharmacology of this novel indole-derived compound. In the present study, the effects of APICA (0 - 1 - 3 mg/Kg, i.p.) were tested in C57BL/6J mice, in a battery of tests that are sensitive to the effects of psychoactive cannabinoids, including body temperature; locomotor a…

Chronic l-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats

Abstract The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the left medial forebrain bundle and 3 weeks treatment with l -DOPA of normal and 6-OHDA lesioned rats on CB1r mRNA expression was investigated by in situ hybridization. A 6-OHDA lesion of nigrostriatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA, did not alter CB1r mRNA levels in the dopamine depleted striatum. Similarly, chronic l -DOPA treatment of normal rats had no effect on striatal CB1r mRNA expression. In contrast, chronic l -DOPA treatment of 6-OHDA-lesioned rats significantly increased CB1r mRNA expression in the denervated striatum. These results suggest that the CB1r activity ma…

Perinatal treatment with 5-methoxytriptamine affects cognition and behavioural reactivity in the juvenile male rat progeny: influence of maternal separation

Reward networks changes in the brain of pathological gamblers: a resting state functional magnetic resonance imaging study

Aims and objectives Methods and materials Results Conclusion Personal information References

Single intense prenatal stress reduce behavioural suppression in an operant conflict paradigm in the adult progeny. Influence of Metyrapone administration

Stressors presented during late prenatal period can have long-term effects on offspring behaviour (1). Indeed we showed that in the rat progeny a single immobilization procedure at gestational day 16 enhances spatial learning in a non-aversive, rewarded-facilitated learning task, the Can Test, and decreases anxiety-like behaviour in the elevated plus maze (2). In this study, we wanted to investigate: (i) the effects of a single prenatal immobilization-stress on the operant conflict task (OCT), an anxiety-related procedure, in which positively reinforced responses are suppressed by contingent punishment (3); (ii) the expression of mineralcorticoid and glucocorticoid receptors (MRs, GRs) in t…

PATHOLOGICAL GAMBLING: AN ASSOCIATION WITH ALEXITHYMIA, PERSONALITY DISORDERS AND CLINICAL SYNDROMES

Pathological gambling (PG) is a disorder recently conceptualized as a behavioural addiction, because of its neurobiological, neurophysiological and psychological features (American Psychiatric Association. Diagnostic and statistical manual of mental disorders - 5th ed., 2013; Potenza et al., 2012). PG represents both a social and a sanitary cost, in terms of pharmacological and psychological therapies. The aim of this study was to examine the correlation between personality disorders, clinical syndromes and alexithymia levels in a group of pathological gamblers. Furthermore this study aimed at highlighting a relationship between PG and alexithymia, over and above the relationship between pe…

Perinatal Treatment with 5-metoxytriptamine affects cognition and behavioural reactivity in the juvenile male rat progeny; influence of maternal separation

Cannabinoid-‐mediated modulation of hippocampal hyperexcitability: focus on the interplay with nitrergic system in different rat models of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of partial complex seizure in adulthood [1]. Within the framework of hyperexcitability, growing interest has risen on the impact of cannabinoids on the control of paroxysmal phenomena [2], despite their reputation as psychotropic substances with addictive properties [3; 4]. In this regard, it was reported that the on-demand production of endocannabinoids from over-activated postsynaptic cells inhibits neurotransmitter release, hence protecting against excitotoxicity in the hippocampus [5; 6]. Nonetheless, the potential anticonvulsant action of cannabinoids has not been fully addressed. Indeed, CB-mediated effects in animal models are attr…

Nitric oxide influence on hippocampal hyperexcitability: in vivo and in vitro comparative electrophysiological study in the rat

A new “sudden fright paradigm” to explore the role of (epi)genetic modulations of the DAT gene in fear-induced avoidance behavior

Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT-KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive-like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX-HET), compared to HET rats born from WT-mother and KO-father (MAT-HET), implementing the role of maternal care on DAT modulation. We developed a "sudden fright" paradigm (based on dark-light test) to study reaction to fearful inputs in the DAT-KO, MAT-HET, MIX-HET, and WT groups. Rats could freely explore the whole 3-chambers apparatus; then, they wer…

Gender-related effects on emotionality, learning and memory performance in adult rats

Modulation of alcohol consumption using an operant self-administration paradigm: effects of a new dopamine aminoacidic conjugate, Phenylalanine-β(3,4dihydroxyphenyl)-etilamide.

Rewarding and reinforcing properties of alcohol have been shown to be mediated by activation of the mesolimbic dopaminergic system. Experimental evidences suggest that mesolimbic dopamine system is hypofunctional in addicted brain; further, reduced dopaminergic activity outlasts somatic signs of withdrawal and may drive craving and relapse. Boosting strategy on dopaminergic neurons could represent a valid therapy. Effects of pharmacological manipulation of brain Dopaminergic receptors by a new dopamine conjugate, Phenylalanine-β(3,4dihydroxyphenyl)-etilamide (DA-Phen), on operant behaviour and on both acute and prolonged withdrawal symptoms during ethanol abstinence have been evaluated. Mal…

Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets

Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia while repeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntary movements. The occurrence of dyskinesia has been associated with an altered balance between the direct and indirect striatal output pathways. Using in situ hybridisation histochemistry, we now compare the effects of these drug treatments on striatal preproenkephalin-A (PPE-A) and adenosine A(2a) receptor mRNA expression as markers of the indirect pathway and striatal preprotachykinin (PPT) mRNA and preproenkephalin-B (PPE-B, prodynorphin) mRNA expression as markers of the d…

Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats

Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize…

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95…

Manipulation of the DA signal on the onset of relapse of ACD

It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara, 1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drug withdrawal in animal studies (Weiss F et al. 1992; 1996). Experimental evidences have proven D2 receptor involvement in drug s…

[3H]-DA release evoked by low pH medium and internal H+ accumulation in rat hypothalamic synaptosomes: involvement of calcium ions

The pH fluctuations have been often interpreted as an insufficient regulation or as a consequence of the onset of pathological events, such as ischemia, in which a significant decrease in pH levels occurs. Neurotransmitter release appears to be affected by pH drop significantly. In this study, we investigated the effect of an extracellular and an intracellular acidification on tritiated dopamine release ([3H]-DA release), from superfused rat hypothalamic synaptosomes. When compared to basal release, extracellular acidification, due to a reduction in the external pH of the nominally carbonic-free superfusion media, provoked a significant increase in [3H]-DA release that showed a sensitivenes…

Reward-related limbic memory and stimulation of the cannabinoid system: An upgrade in value attribution?

While a lot is known about the mechanisms promoting aversive learning, the impact of rewarding factors on memory has received comparatively less attention. This research investigates reward-related explicit memory in male rats, by taking advantage of the emotional-object recognition test. This is based on the prior association, during conditioned learning, between a rewarding experience (the encounter with a receptive female rat) and an object; afterwards rat discrimination and recognition of the â emotional objectâ is recorded in the presence of a novel object, as a measure of positive limbic memory formation. Since endocannabinoids are critical for processing reward and motivation, the co…

Effects of prenatal acute stress on the behavioural reactivity in handled and non-handled rat progeny

The effects of prenatal stress are dependent on the intensity and duration of the stress treatment: chronic, uncontrollable stress causes an impairment in the normal adaptive responses to physical and physiological stimuli whereas acute and mild stress facilitates the morphological development of fetal brain neurons. The presents study was designed to investigate whether a single stress exposure during pregnancy may exert a facilitatory effect on the behaviour of the juvenile progeny. The effects of a postnatal handling procedure have been also investigated. One-month prenatally stressed rats (PSR) whose dams had been restrained for 120 minutes at the 16th day of gestation, showed an increa…

Mothering under the influence: How perinatal drugs of abuse alter the mother-infant interaction

AbstractAlthough drug-abusing women try to moderate their drug and alcohol use during pregnancy, they often relapse at a time when childcare needs are high and maternal bonding is critical to an infant’s development. In the clinical setting, the search for the neural basis of drug-induced caregiving deficits is complex due to several intervening variables. Rather, the preclinical studies that control for drug dose and regimen, as well as for gestational and postpartum environment, allow a precise determination of the effects of drugs on maternal behaviour. Given the relevance of the issue, this review will gather reports on the phenotypic correlates of maternal behaviour in preclinical stud…

Acetaldehyde Oral Self-Administration: Evidence from the Operant-Conflict Paradigm

Background: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. Methods: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenanc…

The role of pregnenolone sulphate in spatial orientation-acquisition and retention: An interplay between cognitive potentiation and mood regulation

Abstract Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s. c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study. Furthermore, on the basis of PREGS pharmacological profile, the modulation of depressive-like behaviour was also evaluated in the forced swim test (FST). Our…

Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease

Background: Aβ 1-42 peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Methods: A rat model of AD was obtained by intra-hippocampal injection of Aβ 1-42 peptide (23 μg/2 μl). After 6 days, 3.6 μg of IFNβ1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or …

Serotonergic modulation of rat pineal gland activity: in vivo evidence for a 5-Hydroxytryptamine(2C) receptor involvement

There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT(2) receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal …

Repeated and single prenatal stress differently affect stress reactivity and learning performance in adolescent male rats

Hippocampal reversible lesions in a case of transient global amnesia

We report the case of 55-year-old man that after an emotional stress showed retrograde and anterograde amnesia with impairment of orientation in space and time but undisturbed consciousness. A neurological examination excluded other neurological signs or symptoms. The amnesic syndrome resolved spontaneously within 24 hours and the hypothesis of transient global amnesia was placed. Brain CT scan and conventional MRI sequences did not show any relevant pathological findings but diffusion-weighted imaging (DWI) showed two millimetric bright spot of restricted diffusion in the right hippocampus; in a brain MRI follow-up those findings were no more appreciable. The diagnosis of transient global …

Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevate…

Sexually dimorphic effects of alcohol self-administration on cognitive processes

Chronic alcohol consumption is able to modify cognitive and emotional behaviour in humans. Many studies on gender diversity have identified swingeing differences between man and woman, not only in the propensity for alcohol abuse, but also in their behavioural effects. In this study we investigate in adult male and female rats: i) alcohol drinking behaviour and preference pattern using a 3-bottle choice paradigm with water, 10% ethanol solution and white wine (10%v/v), along a four-week period; ii) Alcohol free access (AFA) effects on locomotion and behavioural reactivity in the Open Field; iii) The influence of AFA on spatial learning and reference memory, employing the Morris Water Maze. …

Antiepileptic effect of dimethyl sulfoxide in a rat model of temporal lobe epilepsy.

Dimethyl sulfoxide (DMSO) is an amphipathic molecule widely used to solubilize water-insoluble compounds. In many studies it was reported that DMSO is capable of affecting several biological processes, thus resulting in a potential cause for the misinterpretation of experimental data. Recent papers showed that DMSO modified the brain bioelectric activity in animal models of epilepsy. In an in vivo model of temporal lobe epilepsy in the rat, we examined the effects of different doses (10%, 50% and 100%) of DMSO on the maximal dentate activation (MDA). The results show that DMSO induced a dose-dependent significant reduction of the electrically induced paroxysmal activity.

Impact of a single, intense prenatal stress on ethanol drinking behaviour and cognition in adult male rats

Early exposure to stressful stimuli is crucial for developing varied behavioural patterns in adulthood such as anxiety, cognitive dysfunction and abuse disorders. The alteration of the hypothalamic–pituitary–adrenal (HPA) axis represents the neurobiological substrate responsible of the behavioural consequences of prenatal stress (PS). Indeed, prenatal manipulation of the HPA axis impacts on cognitive performance of the adult offspring, but also on vulnerability to alcohol consumption. Prenatal acute, moderate restraint stress has proved to facilitate HPA axis development of the offspring, since maternal corticosterone secretion leads to the reduction of anxiogenic behaviour and an improveme…

Increased neuropeptide Y mRNA expression in striatum in Parkinson's disease.

High levels of neuropeptide Y (NPY) are found in basal ganglia where it is co-localised with somatostatin (SOM) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH/d) in a population of striatal GABA containing interneurones. Although alterations occur in the levels of various neuropeptides in basal ganglia in Parkinson’s disease (PD), it is not known whether NPY is affected. Using in situ hybridisation immunohistochemistry, we have examined the distribution of NPY mRNA in the caudate nucleus, putamen and nucleus accumbens of normal individuals and patients with PD. NPY mRNA was weakly expressed in the caudate nucleus, putamen and nucleus accumbens in normal individuals with a…

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study

Background Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving. Aims In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve …

A new dopamine amino-acid conjugate: preclinical in vitro studies and evaluation of behavioural effects in rats

It is well established that alterations in the functionality of dopaminergic transmission are associated with neurodegenerative diseases such as Parkinson’s Disease. The purpose of this study was to investigate the activity of a new dopamine amino-acid conjugate: L-phenylalanine-β-(3,4-dihydroxyphenyl) etilamide(DA-Phe) in the central nervous system, by assessing its influence on different behavioural parameters in the rat. Preliminarily, we tested the in vitro stability in plasmatic environment following the disappearance of DA-Phen from human plasma and the concurrent appearance of dopamine. Using rat brain homogenate, we also evaluated the level of DA-Phen cleavage by cerebral enzymes an…

DA-Phen as a new potential DA-mimetic agent for treatment of alcohol addiction: preclinical in vivo studies

Rewarding and reinforcing properties of alcohol are mediated by activation of the mesolimbic dopaminergic system1. This neurosystem is hypofunctional in the addicted brain, even beyond somatic and psychological signs of withdrawal. Boosting strategy on the dopaminergic tone could represent a valid approach to alcohol addiction treatment2. The effects of a new dopamine conjugate3 (2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide, DA-Phen) on operant behaviour and on withdrawal behaviour, following alcohol deprivation, were evaluated. The concentration of acetaldehyde (ACD), ethanol's first metabolite, as an indirect measure of the possible DA-Phen modulation in alcohol consum…

Pyrazolobenzotriazinones Derivatives as COX Inhibitors: Synthesis Biological Activity and Molecular Modeling Studies

Pyrazolylbenzotriazinones are endowed with structural analogy with the COX-2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3-pyrazolyl-substituted benzotriazinones as anti-inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a-c and 18a-c have been prepared by reacting the opportune ethyl 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate or 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5-(4-oxo-1,2,3-benzotriazin-3(4H)-y…

Effects of prenatal treatment with 5-metoxytriptamine on learning performance of juvenile male rat progeny. Influence of maternal separation

Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus

We examined the effects of the endocannabinoide-anandamide (AEA), the synthetic cannabinoid, WIN55,212-2, and the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (4-beta-PMA), on the release of [(3)H]d-Aspartate ([(3)H]d-ASP) from rat hippocampal synaptosomes. Release was evoked with three different stimuli: (1) KCl-induced membrane depolarization, which activates voltage-dependent Ca(2+) channels and causes limited neurotransmitter exocytosis, presumably from ready-releasable vesicles docked in the active zone; (2) exposure to the Ca(2+) ionophore-A23187, which causes more extensive transmitter release, presumably from intracellular reserve vesicles; and (3) K(+) channel block…

Risposte endocrine ed immunitarie in calciatori professionisti dopo allenamento e competizione ufficiale

Binge-like alcohol exposure in adolescence: behavioural, neuroendocrine and molecular evidence of abnormal neuroplasticity … and return

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress

Evaluation of neuropeptide Y expression during acetaldehyde withdrawal in rats. Focus on hippocampus and nucleus accumbens

Stress-related neuropeptides are involved in setting up alcohol addiction. Ethanol is able to acutely induce CRH and ACTH release, while cronically a dampered response of the hypothalamus -pituitary- adrenal (HPA) axis has been observed. Also neuropeptide Y (NPY) has been shown to modulate ethanol consumption, and its central expression seems inversely correlated to ethanol intake. Recent in vivo and in vitro evidence have highlighted the key role of acetaldehyde (ACD), ethanol first metabolite, as a mediator of the central effects of ethanol, even as modulator of the neuropeptidergic transmission in the rat brain. The aim of this study was to investigate NPY immunoreactivity following a 4-…

Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to rveal 5-HT1a receptor function

Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg/kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total d…

The neurosteroids sulphate PREGS and DHEAS exert a facilitative role on learning performance in adult male rats

Prenatal diazepam exposure alters neurosteroid modulation of NMDA receptors regulating noradrenaline release from rat hippocampus

Pregnenolone sulphate faciltates object recognition and reduces depressive-like behaviour in male adult rats

Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two w…

Addictive-like behaviour for Acetaldehyde: involvement of D2 receptors

Acetaldehyde (ACD), ethanol's first metabolite, is centrally active and shows rewarding and motivational properties. It is able to activate mesolimbic dopamine system, since it enhances neuronal firing of dopamine cells in ventral tegmental area and exerts dopamine release in the nucleus accumbens (Foddai et al., 2004; Melis et al., 2007; Deehan et al., 2013). ACD motivational properties are demonstrated by self-administration studies in rodents (Rodd et al., 2005), particularly behavioural evidence suggests that ACD could produce positive reinforcing effects in operant-conflict paradigms (Cacace et al., 2012). In order to shed light on neurobiological substrate underpinning ACD-related beh…

Manipulatios of glucocortioid induced stress response may differently affect the acquisition of a reward-facilitated spatial/visual learning task

Farmacologia Generale

Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.

The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatme…

Acetaldehyde and Motivation

Abstract Acetaldehyde contributes to alcohol’s neuroactive effects through its own motivational properties. This chapter gathers current evidence on acetaldehyde psychoactive action, focusing on behavioral investigations able to unveil acetaldehyde rewarding effects and their pharmacological modulation in vivo. Acetaldehyde induces conditioned place preference for paired environment and cues and is dose-dependently self-administered in a two-bottle choice drinking paradigm. Acetaldehyde’s motivational properties are further highlighted by operant paradigms tailored to model several addiction-like behaviors, such as induction and maintenance of operant responding, drug-seeking in extinction,…

Single, intense prenatal stress decreases emotionality and enhances learning performance in the adolescent rat offspring: Interaction with a brief, daily maternal separation.

Perinatal manipulations can lead to neurobehavioural changes in the progeny. In this study we investigated, in adolescent male rat offspring, the consequences of a single, intense prenatal stress induced by a 120 min-maternal immobilization at gestational day 16, and of a daily, brief maternal separation from postnatal day 2 until 21, on: unconditioned fear/anxiety-like behaviour in open field and in elevated plus-maze; learning performance in the "Can test", a non-aversive spatial and tactile/visual task; corticosterone plasma levels under basal and stress-induced conditions. Our results indicate that both prenatal stress and maternal separation procedures decrease emotionality and enhance…

Drinking pattern matters: effects on maternal care and offspring vulnerability to alcohol in rats

Alcohol drinking during pregnancy and post-partum period is a major concern because of the persistent neurobehavioral deficits in the offspring, which include increased vulnerability to substance abuse (1). The intermittent pattern of alcohol consumption induces higher drinking levels and deeper neurobiological changes in addiction-related brain regions, with respect to traditional free-access paradigms in male rats (2, 3). Nevertheless, no studies investigated on the effects of the drinking pattern on female subjects during pregnancy and perinatal time. To this aim, this study explored the consequences of continuous vs. intermittent drinking pattern on maternal behaviour and on offspring v…

FUNCTIONAL CONNECTIVITY OF THE CEREBELLUM INPATHOLOGICAL GAMBLER

Motor Transitions' Peculiarity of Heterozygous DAT Rats When Offspring of an Unconventional KOxWT Mating.

Abstract Causal factors of psychiatric diseases are unclear, due to gene × environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DAT-KO), has enhanced our understanding into the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessed phenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal” origin (MAT-HET, obtain…

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior durin…

Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenetetrazol.

Abstract Rats were treated for 5 weeks with three subconvulsant doses of picrotoxin (PTX) and pentylenetetrazol (PTZ) per week to induce a persistent reduction of the GABA A receptor function which results in chemical kindling. Fifteen days after termination of this treatment schedule, the effect of desipramine (DMI) and alpraxolam (ALP) on immobility time in the forced swim test (FST) was evaluated. Chronic PTX and PTZ did not alter the immobility time. Acute PTX and PTZ reduced the immobility of rats chronically treated with vehicle but not of those exposed chronically to PTX and PTZ. Chronic PTX did not influence the anti-immobility effect of DMI, but blocked that of ALP. Chronic PTZ mar…

The role of (E)-6-chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2-styrylquinazolin-4(3H)-one in the modulation of cannabinoidergic system. A pilot study

Abstract Background Compounds acting on endocannabinoid system regulate different neuronal processes through the cannabinoid receptors activation. The main aim of this study was determining whether the 2-styrylquinazolin-4(3H)-one 5, a structural analogue of rimonabant, was able to counteract the behavioural signs of the activation of the endocannabinoidergic system induced by CP 55.940. Methods Behavioural assessment was carried out using the tetrad task and the novel object recognition test. The endocannabinoidergic system activation was possible by the administration of CP 55.940 and 30 min after rats were tested in the tetrad task for the evaluation of the antinociceptive-, cataleptic-,…

Behavioural responsiveness to picrotoxin and desipramine in adult rats prenatally exposed to different benzodiazepine receptor agonists

The behavioural responsiveness to picrotoxin and desipramine was investigated in adult rats prenatally exposed to different benzodiazepine receptor agonists such as diazepam, alprazolam and zolpidem. Prenatal exposure to diazepam and alprazolam similarly potentiated the anti-immobility effect on the forced swimming test and the inhibitory effect on spontaneous motor activity of picrotoxin and desipramine and increased the seizure sensitivity to picrotoxin. Prenatal zolpidem seems to be ineffective. These data suggest that, despite the differences in their pharmacodynamic profile, prenatal exposure to diazepam and alprazolam, but not zolpidem, may have similar permanent consequences on the b…

Ethanol Modulates Corticotropin Releasing Hormone Release From the Rat Hypothalamus: Does Acetaldehyde Play a Role?

BACKGROUND AND METHODS Ethanol (EtOH) activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropin hormone, glucocorticoid release, and in modifications of the response of the axis to other stressors. The initial site of EtOH action within the HPA system seems to be the hypothalamus. Thus, to determine the mechanisms responsible for these effects, we investigated: (i) whether EtOH was able to release corticotrophic releasing hormone (CRH) from incubated hypothalamic explants; (ii) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in EtOH activity. To this aim, rat hypothalamic explants were incubated with: (…

Behavioural stress reactivity in handling naive and handling-habituated adult male rats prenatally exposed to different benzodiazepine receptor agonists

Gender related effects of pregnenolone sulfate on behavioural reactivity and learning performance in prenatally diazepam-treated rats.

Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats.

In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learnin…

EFFECTS OF SHIFT WORK ON CARDIOVASCULAR ACTIVITY, SERUM CORTISOL AND WHITE BLOOD CELLS COUNT IN A GROUP OF ITALIAN FISHERMEN

We analyzed the effects of working activity and working shifts on the circadian rhythmicity and circadian phase relations of serum cortisol level, white blood cells count, resting heart rate and systolic/diastolic blood pressure in a group of italian fishermen. We observed a shift-induced displacement of cortisol secretion and a modification in leukocyte count. Moreover, systolic/diastolic blood pressure and resting heart rate were markedly influenced by the night shift, whereas no appreciable changes were observed after the morning and afternoon shifts, compared to pre-working values. These data suggest that the human circadian system is greatly influenced by shift work, and serum cortisol…

Dopaminergic agents acting at D1 and D2 receptor sites differently affect melatonin synthesis in rat pineal gland during night.

Neurosteroid modulation of the presynaptic NMDA receptors regulating hippocampal noradrenaline release in normal rats and those exposed prenatally to diazepam

Abstract Prenatal exposure to diazepam (DZ), a positive allosteric modulator of the γ-aminobutyric acidA (GABAA) receptor complex, exerts profound effects that become more evident during puberty and in many cases are sex-specific, suggesting that such exposure interferes with the activity of steroid hormones. Apart from their well known effects on the genome, the reduced metabolites of many steroid hormones also interact directly with membrane receptors, including those for N-methyl- d -aspartate (NMDA). In this study, we compared the effects of several neurosteroids on NMDA receptors from normal rats and those exposed in utero to DZ (1.25 mg/kg per day) from the 14th through the 20th day o…

The neurosteroids DHEAS and PREGS may affect learning performance by altering affective state

Erratum to “Motor Transitions' Peculiarity of Heterozygous DAT Rats When Offspring of An Unconventional KOxWT Mating” [Neuroscience 433C (2020) 108–120]

The role of neurosteoids sulphate in a spatial and object recognition learning task

The term “neuroactive steroid” refers to steroids that have rapid modulatory effects on ligand-gated ion channels via non-genomic mechanism. Specifically, neurosteroids can alter neuronal excitability via the cell surface interacting with specific neurotransmitter receptors. The neurosteroid pregnenolone sulphate (PREGS) has been described as negative modulator of GABAA receptor and positive modulator of NMDA receptor, affecting cognition as well as emotionality. The present study was aimed to assess the effects of the acute administration of PREGS (10 mg/Kg, s. c.) on rats cognitive functions using a novel task, the Can test. This task explores, under reinforcement, the spatial/visual cues…

Gender-related affects of pregs on emotional, learning and memory performance in adult rats

ETHANOL DRINKING PATTERN DIFFERENTLY AFFECTS NOVELTY-RELATED BEHAVIOUR DURING ABSTINENCE IN FEMALE RATS

Withdrawal from chronic ethanol leads to a multifaceted syndrome, characterized by negative affective state. Novelty seeking and motivation, closely related to affective state, can be assessed in rodents exploring behavioural response to novelty. This study aims at assessing novelty-related behaviour in female rats during ethanol withdrawal following different self-administration patterns. Female rats underwent 9-week-, 2-bottle choice-, continuous or intermittent (3 days/week) access to 20% ethanol; they were named CARs and IARs respectively. After 12h from last ethanol access, they were tested for locomotor activity induced by a novel environment; time spent in the central area of an open…

Non-alcoholic Wernicke's encephalopathy: From MRI findings of a case to differential diagnosis checklist

Wernicke's encephalopathy is a serious neurological disorder secondary to thiamine deficiency in alcoholics. However, rarely it affects non-alcoholics. Here we present a case of Wernicke's encephalopathy in a non-alcoholic 56-year-old female, treated by endoscopic surgery for a duodenal ulcer two years before. She came to our attention for a sudden onset of a neurological syndrome characterized by visual deficits, diplopia, confusion, spatial disorientation and loss of short-term memory. An MRI scan showed the typical MRI findings of Wernicke's encephalopathy, which are discussed together with the possible differential diagnosis.

Alterations in the Emotional Regulation Process in Gambling Addiction: The Role of Anger and Alexithymia

This study aims at the assessment of alexithymia and anger levels in 100 treatment-seeking pathological gamblers compared with controls, who were matched for age, gender and education. Furthermore a positive correlation between alexithymia, anger and severity of gambling disorder and a relationship between gambling behaviour and anger after controlling for alexithymia, are investigated. Finally the role that gender plays in anger in pathological gamblers was also evaluated. Psychological assessment includes the South Oaks Gambling Screen, State-Trait Anger Expression Inventory-2 and the twenty-item Toronto Alexithymia Scale. Statistical analysis of the results shows a higher level of anger …

The neurosteroids sulfate pregs and DHEAS selectively improve memory retention in adult female rats

Alterations in neuropeptide mRNA expression in the striatum in Parkinson's disease

Intermittent- vs continuous alcohol access in female rats: Effects on deprivation phenotype and maternal behavior as a consequence of the drinking pattern

In male rats, the intermittent alcohol access paradigm produces relevant and specific consequences on neuronal activity and behavior, with respect to traditional free-access paradigms (Carnicella et al., 2014). In order to explore gender-related effects, this study aimed at assessing the consequences of two different patterns of alcohol self-administration on peculiar feminine behavioral repertoire, such as deprivation phenotype and maternal care. Animals underwent long-term, home cage, two-bottle “alcohol (20% v/v) or water” choice regimen, with continuous (7 days a week) or intermittent (3 days a week) access, and were tested for alcohol intake and preference. During acute deprivation, th…

Acetaldehyde, motivation and stress: Behavioral evidence of an addictive ménage à trois

Acetaldehyde contributes to alcohol’s psychoactive effects through its own rewarding properties. Recent studies shed light on the behavioral correlates of acetaldehyde administration and the possible interactions with key neurotransmitters for motivation, reward and stress-related response, such as dopamine and endocannabinoids. This mini review critically examines acetaldehyde psychoactive properties, focusing on behavioral investigations able to unveil acetaldehyde motivational effects and their pharmacological modulation in vivo. Similarly to alcohol, rats spontaneously drink acetaldehyde, whose presence is detected in the brain following chronic self-administration paradigm. Acetaldehyd…

A NEW DOPAMINE-AMINOACID CONJUGATE: SYNTHESIS AND DETERMINATION OF PHYSICO-CHEMICAL PROPERTIES USEFUL TO CROSS THE BBB

Neurosteroid PREGS differently affects learning and memory performance by altering emotionality in a gender-related manner

Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018.In present study, the effects of APICA (1-3 mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3 mg/kg, i.p.) or the CB2 antagonist AM630 (3 mg/kg, i.p.) was carried out to characterize APICA activity.Our results sho…

DYSPHORIC-LIKE BEHAVIOUR DURING ETHANOL WITHDRAWAL IN FEMALE RATS. EFFECT OF CONTINUOUS VS INTERMITTENT ACCESS PARADIGM.

Women show higher vulnerability for neuroadaptation to alcohol, which may contribute to negative emotional state during withdrawal (Sharrett-Field et al., 2013; Koob and Le Moal, 1997). This study aimed at exploring the effects of different patterns of voluntary ethanol consumption on female rat"s affective behaviour during withdrawal. Female rats underwent 12-week-, 2-bottle choice- continuous or intermittent (3 days/week ) access to 20% ethanol and were respectively named CARs and IARs. They were tested for alcohol preference; dysphoric-like state during withdrawal (24-48h); depressive- and anhedonic-like behaviours explored by forced swim- and saccharin preference tests; anxiety-like beh…

Acetaldehyde as a drug of abuse: Involvement of endocannabinoid- and dopamine neurotransmission

Acetaldehyde (ACD), the first metabolite of ethanol, directly enhances dopamine neurotransmission (1) and has rewarding and motivational properties in paradigms tailored for studying addictive-like behaviours (2, 3). The endocannabinoid system affects distinct drug-related behaviours, since it may in turn fine-tune dopamine cell activity (4, 5). In light of this, the present study aimed at investigating the effects of a direct manipulation of the DAergic synapse, and the contribution of the endocannabinoid system on oral ACD self-administration in rats. ACD drinking-behaviour was evaluated in an operant paradigm consisting of acquisition and maintenance; extinction; deprivation and relapse;…

Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens

Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modeling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males. Here we investigated the effects of SCVS on pre- and post-synaptic prote…

Perinatal alcohol intake, maternal behaviour and transgenerational inheritance of drug abuse; effects of drinking pattern and environmental enrichment

Alcohol drinking during pregnancy and post-partum is a major concern because of the persistent neurobehavioral deficits in the offspring that include increased vulnerability to substance abuse (McMurray et al., 2008). Moreover, the pattern of alcohol consumption accounts for specific neurobiological alterations that involve brain regions, that significantly overlap with those involved in maternal care behaviour (Stuber et al., 2008; George et al. 2012). Rodent studies on environmental enrichment have clearly demonstrated the capacity for non-drug modification of addiction-related behaviours (Nader et al., 2012). Thus, this study aimed at: (I) exploring the consequences of continuous vs. int…

Prenatal exposure to diazepam and alprazolam, but not to zolpidem, affects behavioural stress reactivity in handling-naïve and handling-habituated adult male rat progeny.

A gentle long-lasting handling produces persistent neurochemical and behavioural changes and attenuates the impairment in the behavioural reactivity to novelty induced by the prenatal exposure to diazepam (DZ) in adult male rat progeny. This study investigated the consequences of a late prenatal treatment with three GABA/BDZ R agonists (DZ) alprazolam (ALP) and zolpidem (ZOLP)), on different stress-related behavioural patterns, in non-handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male rats exposed to forced swim test (FST), acoustic startle reflex (ASR) and Vogel test (VT). The effects on motor activity were evaluated in the open field and in the Skinner box…

GDNF reverses priming for dyskinesia in MPTP-treated, L-DOPA-primed common marmosets

Parkinson's disease (PD) is associated with a progressive loss of dopamine neurons in the substantia nigra and degeneration of dopaminergic terminals in the striatum. Although L-DOPA treatment provides the most effective symptomatic relief for PD it does not prevent the progression of the disease, and its long-term use is associated with the onset of dyskinesia. In rodent and primate studies, glial cell line-derived neurotrophic factor (GDNF) may prevent 6-OHDA- or MPTP-induced nigral degeneration and so may be beneficial in the treatment of PD. In this study, we investigate the effects of GDNF on the expression of dyskinesia in L-DOPA-primed MPTP-treated common marmosets, exhibiting dyskin…

DA-Phen, a new dopamine aminoacid conjugate: in vivo testing and molecular modeling as dopaminergic modulator

Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function

Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg/kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total d…

The endocannabinoid-alcohol crosstalk: Recent advances on a bi-faceted target

Increasing evidence has focusesed on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. In addition, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles i…

Gender-related effects of PREGS on emotionality, learning and memory performance in adult rats.

Activity of orally self-administered acetaldehyde in an operant/conflict paradigm in rats; involvement of cannabinoid cb1 receptors

Acetaldehyde (ACD), ethanol first metabolite, interacts with the dopaminergic reward system, and with the neuropeptidergic transmission in the hypothalamus. Self-administration within operant conditioning is a valid model to investigate drug-seeking and drug-taking behaviour in rats. Cannabinoid CB1 receptors are involved in reinstatement of alcohol-seeking behaviour and of many other drugs of abuse (3). Accordingly, this study was aimed at the evaluation of: 1) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behaviour; 2) the onset of a relapse drinking behaviour, following ACD deprivation; 3) ACD effect in a conflict situation employing the …

Inhibition by Anandamide and Synthetic Cannabimimetics of the Release of [3H]d-Aspartate and [3H]GABA from Synaptosomes Isolated from the Rat Hippocampus

Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K +-evoked release of [ 3H]d-aspartate ([ 3H]d-ASP) and [ 3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [ 3H]d-ASP and [ 3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2′- chloroethyla…

Gender related effects of pregnenolone sulfate on behavioural reactivity and learning performance in prenatallly diazepam-treated rats

DESCRIZIONE DI UN CASO DI LESIONE REVERSIBILE DELLO SPLENIO DEL CORPO CALLOSO IN PAZIENTE CON MONONUCLEOSI INFETTIVA DA COINFEZIONE EPSTEIN-BARR VIRUS (EBV) E CITOMEGALOVIRUS (CMV)

SCOPO Presentiamo un caso di encefalite virale con lesione reversibile dello splenio del corpo calloso (SCC) in un ragazzo di 16 anni con mononucleosi infettiva da coinfezione Epstein-Barr Virus (EBV) e Citomegalovirus (CMV). MATERIALI E METODI Il paziente, a causa della comparsa improvvisa di stato confusionale, irrigidimento e movimenti involontari alternati a tremori in corso di mononucleosi infettiva, giungeva in PS, dove eseguiva una TC encefalo (Siemens SOMATOM Definition AS+ - 128 strati) in condizioni di base ed in tecnica sequenziale, che non evidenziava reperti significativi. Veniva quindi ricoverato con il sospetto di encefalite virale e, il giorno successivo, veniva sottoposto a…

The use of the Emotional-Object Recognition as an assay to assess learning and memory associated to an aversive stimulus in rodents

Abstract Background Emotionally salient experiences induce the formation of explicit memory traces, besides eliciting automatic or implicit emotional memory in rodents. This study aims at investigating the implementation of a novel task for studying the formation of limbic memory engrams as a result of the acquisition- and retrieval- of fear-conditioning – biased declarative memory traces, measured by animal discrimination of an “emotional-object”. Moreover, by using this new method we investigated the potential interactions between stimulation of cannabinoid transmission and integration of emotional information and cognitive functioning. New method The Emotional-Object Recognition task is …

Secretogranin II mRNA expression is increased in Parkinson disease and in MPTP-treated marmosets exposed to chronic L-Dopa administration

Effects of a single intense prenatal stress on emotionality and learning performance in adolescent male rat progeny.Influence of a daily short-term maternal separation.

Chronic perinatal treatment with 5-methoxytryptamine reduces depressive-like behaviour induced by forced swim in mature male rats

ETHANOL PREFERENCE DURING PREGNANCY AFTER LONG-TERM ETHANOL CONSUMPTION: EFFECT OF DRINKING PATTERN AND MATERNAL BEHAVIOUR ANALYSIS

Several studies suggest that pregnancy can reduce ethanol preference and consumption in rats and mice when self-administration starts early during pregnancy (Randall et al., 1980; Means and Goy, 1982). Our first aim was to explore the effect of pregnancy on long-term habit to ethanol, in female rats subjected to 12-week continuous or intermittent (3 days/week) access to 20% ethanol; they were named CARs and IARs respectively. The second aim was to observe their maternal behaviour. Rats were deprived from ethanol during mating and the first gestational week, and then re-exposed to respective ethanol self-administration schedule, starting from the second week of pregnancy. Maternal behaviour …

Gender-related effects on emotionality, learning and memory performance in adult rats. 33° Congresso Società Italiana Farmacologia.

23. Resting state functional magnetic resonance imaging analysis of the brain of pathological gamblers

Purpose Gambling disorder has been recently reclassified under the category “substance-related and addictive disorders”. Recent studies performed through functional MRI (fMRI) have shown that the perseverance of some behaviors can alter brain activation [1] , [2] . In this work we aim at investigating functional connectivity changes in pathological gamblers (PGs) in comparison to healthy controls (HCs) by means of resting state functional Magnetic Resonance Imaging (rs-fMRI). Methods and materials Thirteen HCs and fourteen PGs were recruited (all right handed males; drugs free; mean age 36 ± 10 yrs). All acquisitions were performed through a 1,5 T MRI scanner using a 8-channels phased-array…

PHARMACOLOGICAL MODULATION OF OPERANT BEHAVIOUR FOR ACETALDEHYDE. INVOLVEMENT OF D2 AND CB1 RECEPTORS.

Acetaldehyde (ACD), the first metabolite of ethanol, has rewarding and motivational properties, as shown by behavioural studies specifically tailored for studying addictive-like behaviour (1, 2). The rewarding and incentive effects of alcohol and others addictive substances, result from their capability to enhance mesolimbic dopamine (DA) transmission, as well as to affect the cannabinoid system, which is able to fine-tune the activity of DA neurons (3). ACD directly increases DA neurotransmission (4), but the neural underpinning the operant behaviour for oral-self administered ACD still remains poorly understood. Since D2 and CB1 receptors are involved in alcohol addiction (3), as well as …

Acetaldehyde operant self-administration in rats: focus on D2-receptor activation.

Acetaldehyde (ACD), ethanol first metabolite, is rewarding in rodents and humans; it induces “place preference”, is self-administer directly in the VTA, orally in an operant/conflict paradigm and increases DA neurons’ firing. This research aims at investigating DA2-receptor role in the reinstatement of acetaldehyde operant-drinking behaviour, following induction, maintenance and abstinence in the rat. Male Wistar rats are trained to orally self-administer ACD solution (3.2% v/v) or water, in an operant chamber under a FR1. Afterwards animals undergo cyclic periods of deprivation and relapse to ACD. The effect ofD2-receptor activation by quinpirole (0.03mg/kg,i.p.) on operant ACD self-admini…

The neurosteroids PREGS and DHEAS selectively improve memory retention in adult female rats.

Is Acetaldehyde a substance of abuse? Evidence from a free-access, three-bottle choice paradigm

At present, neuroscience literature dealing with Acetaldehyde (ACD), ethanol first metabolite, as a drug of abuse, reported conditioned taste aversion paradigm and conditioned place preference, following ICV or i.p. administration. No reports exist on ACD oral self-administration probably because of its high volatility. For this reason, this pilot study was aimed at the evaluation of ACD concentration in aqueous solutions, and consequently to the rat drinking behaviour when acetaldehyde was presented in a free-access paradigm together with water and a sweet solution. Preliminarly we investigated the loss of ACD content in aqueous standard solutions. For the investigation of ACD concentratio…

Neurosteroid PREGS differently affects learning and memory performance by altering emotionality in a gender-related manner. 4th International Meeting Steroids and Nervous System, Torino, Italy. Febbrary 17-21 (2007)

Brief maternal separation procedures occurring early in life affect learning and memory in adult Wistar rats: sex-related differences in cognitive behaviour

Adverse life events during the neonatal period result in long-term effects on physiology and behavior. Early postnatal experiences, such as a modification of the mother–infant interaction, may influence the development of neural systems that underlie the expression of neuroendocrine and behavioural responses to environmental challenges. The present study was carried out to investigate the consequences of a brief, maternal separation on declarative and spatial memory, focusing on sex related alteration due to the discrete effects that hormones may play on the brain circuits. Our results indicate that a brief, daily maternal separation results in sexually-dimorphic cognitive alterations that …

Dopamine restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats

Alcohol abuse leads to aberrant forms of emotionally salient memory, i.e., limbic memory, that promote escalated alcohol consumption and relapse. Accordingly, activity-dependent structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing chronic alcohol consumption. Here we show that alcohol-dependent male rats fail to perform an emotional-learning task during abstinence but recover their functioning byl-3,4-dihydroxyphenylalanin (l-DOPA) administration during early withdrawal.l-DOPA also reverses the selective loss of dendritic “long thin” spines observed in medium spiny neurons of the nucleus accumbens (NAc) shell of alcohol-dependent rats d…

6-Hydroxydopamine lesioning differentially affects α-synuclein mRNA expression in the nucleus accumbens, striatum and substantia nigra of adult rats

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion and/or repeated administration of levodopa (L-DOPA) to normal and 6-OHDA-lesioned rats on alpha-synuclein mRNA expression was investigated by in situ hybridization histochemistry. A 6-OHDA lesion of the nigro-striatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA expression, markedly decreased alpha-synuclein mRNA in the lesioned substantia nigra (SN). In contrast, the levels of alpha-synuclein mRNA in the denervated striatum and nucleus accumbens were not altered. Chronic administration of L-DOPA to normal or 6-OHDA-lesioned rats had no effect on alpha-synuclein mRNA expression in the SN, striatum or nu…

Acetaldehyde as the first hit of addictive behaviour

Unhealthy alcohol use is common in the Western society, which puts risk of health consequences, causing multiple behavioural injuries. Increasing evidence focuses on acetaldehyde, the first metabolite of ethanol, as the mediator of the several behavioural actions of alcohol, including its rewarding and motivational effects. In particular, acetaldehyde induces dopamine release in the nucleus accumbens modulating primary alcohol rewarding effect, drug seeking, and relapse behaviour. Recent behavioural studies point at acetaldehyde as a drug of abuse since its oral self-administration is induced and maintained in an operant/conflict paradigm. These findings provide further evidence on the role…

Effects of prenatal treatment with 5-methoxytryptamine on learning performance of juvenile male rat progeny. Influence of maternal separation

Prenatal diazepam exposure functionally alters the GABA(A) receptor that modulates [3H]noradrenaline release from rat hippocampal synaptosomes.

In rats, exposure to diazepam (DZ) during the last week of gestation is associated with behavioral alterations (in some cases sexually dimorphic) that appear when the animals reach adulthood. This study was conducted to evaluate the effects of prenatal DZ exposure on the function of the gamma-aminobutyric (GABA)(A) receptor complex. The method used - perfusion of rat hippocampal nerve terminals labeled with [3H]noradrenaline (NA) - allowed us to evaluate the effects of DZ on a specific native GABA(A) receptor subtype which is located on hippocampal noradrenergic nerve endings and mediates the release of NA. Muscimol stimulated synaptosomal release of [3H]NA in a concentration-dependent mann…

NMDA-GABA interactions in an animal model of behaviour: a gating mechanism from motivation toward psychotic-like symptoms

We studied the effects of desipramine, alprazolam, muscimol and dizocilpine (MK-801) (alone or associated with desipramine) in the forced swimming test in rats after long-lasting termination of chronic exposure to vehicle and pentylenetetrazol. Sensitisation with pentylenetetrazol was ineffective in changing immobility time in the forced swimming test compared to vehicle treatment; pentylenetetrazol enhanced the anti-immobility effect of desipramine, abolished the anti-immobility effect of alprazolam and did not affect the anti-immobility effect of muscimol. MK-801 at the dose that did not modify immobility time in vehicle-treated rats and in pentylenetetrazol-treated animals strongly poten…

Social Interactions of Dat-Het Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

Social interaction is essential for life but is impaired in many psychiatric disorders. We presently focus on rats with a truncated allele for dopamine transporter (DAT). Since heterozygous individuals possess only one non-mutant allele, epigenetic interactions may unmask latent genetic predispositions. Homogeneous “maternal” heterozygous offspring (termed MAT-HET) were born from dopamine-transporter knocked-out (DAT-KO) male rats and wild-type (WT) mothers

Pregnenolone sulphate (PREGS) affects spatial learning and memory in two different cognitive tasks in adult rats. Influence of the emotional state.

Pregnenolone sulphate (PREGS) is one of the most potent memory-enhancing neurosteroids in rodent learning studies, also involved in the modulation of the emotional state (Valleè et al 2001). Neurosteroids exert an important role as modulators of the neuronal activity by interacting with different receptors or ion channels (Urani et al 1998). Indeed PREGS acts as negative modulator of GABAA- and as positive modulator of NMDA -receptors. Altered levels of PREGS have also been reported during aging and in human neurodegenerative pathologies like Alzheimer’s disease. The aim of this study was to investigate, in adult male rats, the effects of a single injection of PREGS (10 mg/kg s.c.) on: i) o…

Adolescent binge-like alcohol exposure dysregulates NPY and CGRP in rats: Behavioural and immunochemical evidence.

Alcohol binge drinking during adolescence impacts affective behaviour, possibly impinging on developing neural substrates processing affective states, including calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY). Here, we modelled binge-like alcohol exposure in adolescence, by administering 3.5 g/kg alcohol per os, within 1 h time, to male adolescent rats every other day, from postnatal day 35 to 54. The effects on positive and negative affective behaviour during abstinence were explored, including consummatory behaviour and weight gain; social behaviour in the modified social interaction test; thermal nociception in the tail-flick test; psychosocial stress coping in the reside…

Ethanol releases corticotropic releasing hormone (CRH) from rat hypothalamic explants; role of acetaldehyde

Ethanol activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropic hormone (ACTH) glucocorticoid release, and a modification of the response of this axis to other stressors (Lee et al 1999, 2000). To determine the mechanisms responsible for these effects we investigated : 1) whether ethanol was able to release CRH from incubated hypothalamic explants; 2) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in ethanol effects. To this aim, rat hypothalamic explants were incubated with: 1) medium containing ethanol at 150 mg %; 2) different concentrations of ACD (4.4, 13.2, 44, 132 x 10-3 mg%); 3) ethanol plus …

Evaluation of chronic alcohol self-administration in male and female rats using a 3-bottle choice paradigm. Sexually dimorphic effects on spatial learning and reference memory

Detection of a temporal structure in the rat behavioural response to an aversive stimulation in the emotional object recognition (EOR) task.

Abstract Aim of the research was to investigate whether a temporal structure could be detected in the behavioural response to an aversive stimulation. A fear-related memory task was used in rats, placed in a modified version of the Novel Object Recognition task known as Emotional Object Recognition task, i.e. a behavioural assay that orbits around the declarative memory for an aversive experience. To this purpose, twelve male Wistar rats, divided in two groups (Control and Aversive memory), observed after 4 h (OR4h) and after 24 h (OR24h) from the delivery of an aversive stimulation, associated to a specific object, were used. Data were evaluated both in terms of conventional quantitative a…

Single intense prenatal stress can differently affect emotional behavior according to the nature of the task. Influence of metyrapone

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18–20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Invento…

SY26-2ACETALDEHYDE ENDOCANNABINOIDS AND DOPAMINE: IS THIS –JUST- “A MENAGE A TROIS”?

As ethanol, its first metabolite, acetaldehyde (ACD), enhances dopamine neurotransmission and exerts rewarding and motivational effects in animal models tailored for studying addictive-like behaviours. The endocannabinoid system fine-tuning dopamine cell activity, affects distinct drug-related behaviours and specific drug-induced effects. In light of this, it becomes urgent to investigate the implications of …

The neurosteroids sulfate PREGS and DHEAS exert a facilitative role in learning performance in adult male rats

THe role of autologous nerve fragments implantation in enhancing peripheral nerve regeneration

ntroduction: The aim of this study was to assess the effect of seeding a nerve suture with autologous nerve fragments. Our hypothesis is that the fragments could improve axonal regeneration. Back to Top | Article Outline Material and Methods: On 20 Sprague-Dawley rats a 15mm sciatic nerve defect was created and grafted. In the study group (n=10) a 1mm nerve segment was minced and seeded around the distal suture. In the control group (n=10) no fragments were seeded. Rats were sacrificed at 4 (n= 10) and 12 weeks (n= 10) and number of regenerated fibers, fiber area and density, Soleus and Gastrocnemius muscles mass indexes, and walking track analysis in the 12 weeks group were evaluated. The …

3H-DA release evoked by low pH medium and internal H+ accumulation in rat hypothalamic synaptosomes

Patterns matter: continuous Vs intermittent access to ethanol differently affects withdrawal behavioural phenotype and maternal care in female rats.

Modeling voluntary ethanol consumption in female rats is crucial for gaining further insight in gender-related vulnerability to alcohol. Since ethanol effects depend not only on the amount consumed, but also on drinking pattern, this study aimed at assessing the influence of continuous and intermittent ethanol self-administration on peculiar aspects of female behavioural repertoire during withdrawal and relapse. Female rats undergoing a 15-week-long, 20% ethanol continuous or intermittent (3days/week) access, respectively named CARs and IARs, were tested for alcohol intake (gr/kg) and preference. During withdrawal we assessed: novelty and reward preference in novel object exploration and sa…

In utero Δ9-tetrahydrocannabinol exposure confers vulnerability towards cognitive impairments and alcohol drinking in the adolescent offspring: Is there a role for neuropeptide Y?

Background:Cannabinoid consumption during pregnancy has been increasing on the wave of the broad-based legalisation of cannabis in Western countries, raising concern about the putative detrimental outcomes on foetal neurodevelopment. Indeed, since the endocannabinoid system regulates synaptic plasticity, emotional and cognitive processes from early stages of life interfering with it and other excitability endogenous modulators, such as neuropeptide Y (NPY), might contribute to the occurrence of a vulnerable phenotype later in life.Aims:This research investigated whether in utero exposure to Δ9-tetrahydrocannabinol (THC) may induce deficits in emotional/cognitive processes and alcohol vulner…

EFFECT OF ACETALDEHYDE INTOXICATION AND WITHDRAWAL ON NEUROPEPTIDE Y EXPRESSION. FOCUS ON CB1 RECEPTOR ROLE.

Neuropeptide Y (NPY) acts as an endogenous anxiolytic, and, like endocannabinoids, plays an important role in the regulation of neuronal excitability during ethanol withdrawal (Rubio et al., 2011). Since acetaldehyde is considered a mediator of ethanol central effects, this research aims at investigating, following intoxication and during withdrawal, the effects of acetaldehyde on NPY expression in brain areas particularly vulnerable to alcohol, and the influence of cannabinoid system on it. Rats underwent acetaldehyde intoxication (450mg/kg, i.g., 4 times daily for 4 days); AM281, a CB1 selective antagonist (2,5 mg/kg, i.p.) was administered during abstinence. Immunohistochemical analysis …

Effect of Acetaldehyde on CRF release form incubated hypothalamic explants

In the past, Acetaldehyde (ACD), the main metabolite of ethanol (ETOH), was mainly studied for its toxic and adverse effects (1). However, recently, ACD was reported to determine behavioural and neurochemical effects, following ETOH assumption in rodents (2, 3). Indeed, ACD enhances dopamine levels in nucleus accumbens, stimulates beta-endorphin release from hypothalamic cells, mediating alcohol reinforcing effects (4). Since little is known about the effects of ACD on other central neuropeptides, in this research we aimed to investigate ACD influence on hypothalamic corticotropin-releasing factor (CRF) release. In order to ascertain this hypothesis, different doses of ACD (1, 10, 3x10 micr…

Psychodiagnostic Assessment of Pathological Gamblers: A Focus on Personality Disorders, Clinical Syndromes and Alexithymia

Comorbid psychopathological syndromes are common in pathological gamblers (PGs), but the contribution of alexithymia, as a disorder of affect regulation, has not been fully explored yet. This study sought to examine the association between personality disorders, clinical syndromes and alexithymia levels in a group of PGs and to highlight a relationship between gambling behaviour and alexithymia scores, apart from the relationship between other disorders and gambling behaviour. Psychological assessment included the South Oaks Gambling Screen, Millon Clinical Multiaxial Inventory (MCMI-III) and Toronto Alexithymia Scale (TAS-20) performed on 70 treatment seeking PGs and 70 healthy controls. S…

Both Short- and Long-Acting D-1/D-2 Dopamine Agonists Induce Less Dyskinesia than l-DOPA in the MPTP-Lesioned Common Marmoset (Callithrix jacchus)

Abstract The current concept of dyskinesia is that pulsatile stimulation of D-1 or D-2 receptors by l -DOPA or short-acting dopamine agonists is more likely to induce dyskinesia compared to long-acting drugs producing more continuous receptor stimulation. We now investigate the ability of two mixed D-1/D-2 agonists, namely pergolide (long-acting) and apomorphine (short-acting), to induce dyskinesia in drug-naive MPTP-lesioned primates, compared to l -DOPA. Adult common marmosets ( Callithrix jacchus ) were lesioned with MPTP (2 mg/kg/day sc for 5 days) and subsequently treated with equieffective antiparkinsonian doses of l -DOPA, apomorphine, or pergolide for 28 days. l -DOPA, apomorphine, …

The efficacy of a functional therapy program for gambling disorder: A Pilot study

Background: Despite the great progress achieved by treatment approaches for Gambling Disorder (GD) the relevance of studying efficacious therapies still remains high. This pilot study aims at the evaluation of the efficacy of a standardized protocol based on Functional theory for GD. Functional Therapy (FT) is an integrated body-mind therapy.Methods: Twenty-eight pathological gamblers completed the FT protocol consisted in 16 sessions, two times a week for a total duration of two months, in an individual setting. No one of the patients was taking any psychopharmacological therapy. Psychological assessment both at baseline (T0) and at the end of the treament (T1) includes the South Oaks Gamb…

Vulnerability to alcohol operant-drinking behaviour: implications of environmental stim

Environmental stimuli, occurring early in life, shape the drinking trajectories and the psychopathological outcome of alcohol consumption in adult life. In particular, early perinatal procedures can permanently alter various patterns of drug use and behaviour in rat adulthood (Pryce CR, 2001). Early handling (EH) apparently is responsible for neurochemical and behavioural changes in adulthood, due to boosts in maternal care after daily reunion. It has been suggested that fostered maternal care, in the form of licking and grooming, is a key feature in determining neural changes and offspring fear responses and alter the reward/reinforcement pathway through epigenetic mechanisms that likely u…

Pregnenolone sulphate enhances spatial orientation and object discrimination in adult male rats: Evidence from a behavioural and electrophysiological study

Abstract Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation–acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo , after acute PREGS systemic administration in order to investigate on the neuronal activati…

Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to improve nerve regeneration in rats

Background: The aim of this study was to assess the effect of seeding the distal nerve suture with nerve fragments in rats. Methods: On 20 rats, a 15 mm sciatic nerve defect was reconstructed with a nerve autograft. In the Study Group (10 rats), a minced 1 mm nerve segment was seeded around the nerve suture. In the Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a walking track analysis with open field test (WTA), hystomorphometry (number of myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was used for statistical analysis. Results: At 4 and 12 weeks the Study Gr…

Increased functional connectivity in gambling disorder correlates with behavioural and emotional dysregulation: Evidence of a role for the cerebellum

Gambling disorder (GD) is a psychiatric disease that has been recently classified as a behavioural addiction. So far, a very few studies have investigated the alteration of functional connectivity in GD patients, thus the concrete interplay between relevant function-dependent circuitries in such disease has not been comprehensively assessed. The aim of this research was to investigate resting-state functional connectivity in GD patients, searching for a correlation with GD symptoms severity. GD patients were assessed for gambling behaviour, impulsivity, cognitive distortions, anxiety and depression, in comparison with healthy controls (HC). Afterwards, they were assessed for resting-state f…

Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation.

2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (Pe), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (Pe = 0.32 ± 0.01 × 10(-6 )cm/s). Using the Caco-2 cell system, the Papp AP-BL in absorptive direction (3.36 ± 0.02 × 10(-5 )cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 ± 0.07 × 10(-5 )cm/s), suggesting a polarized transport. The efflux ratio (Papp AP-BL/Papp BL-AP = 0…

Stroke after tadalafil use

No abstract available

Conflict-behaviour and temporal discrimination performance in the rat: Comparison between alprazolam and various conventional benzodiazepines

Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.

Abstract Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these ex…

Pre-conceptional and Peri-Gestational Maternal Binge Alcohol Drinking Produces Inheritance of Mood Disturbances and Alcohol Vulnerability in the Adolescent Offspring

Although binge drinking is on the rise in women of reproductive age and during pregnancy, the consequences in the offspring, in particular the inheritance of alcohol-related mood disturbances and alcohol abuse vulnerability, are still poorly investigated. In this study, we modeled both Habitual- and Binge Alcohol Drinking (HAD and BAD) in female rats by employing a two-bottle choice paradigm, with 20% alcohol and water. The exposure started 12 weeks before pregnancy and continued during gestation and lactation. The consequences induced by the two alcohol drinking patterns in female rats were assessed before conception in terms of behavioral reactivity, anxiety- and depressive-like behavior.…

Predictors of early dropout in treatment for gambling disorder: The role of personality disorders and clinical syndromes

Several treatment options for gambling disorder (GD) have been tested in recent years; however dropout levels still remain high. This study aims to evaluate whether the presence of psychiatric comorbidities predicts treatment outcome according to Millon's evolutionary theory, following a six-month therapy for GD. The role of severity, duration of the disorder, typology of gambling (mainly online or offline) and pharmacological treatment were also analysed. The recruitment included 194 pathological gamblers (PGs) to be compared with 78 healthy controls (HCs). Psychological assessment included the South Oaks Gambling Screen and the Millon Clinical Multiaxial Inventory-III. The "treatment fail…

Environmental enrichment reverts the effects of continuous or intermittent perinatal alcohol exposure. Focus on alcohol vulnerability and affectivity in the offspring

Alcohol consumption during perinatal periods is common, despite the warning of adverse effects on the foetal development. In female rats, the intermittent pattern of alcohol consumption is responsible for higher drinking levels and more profound disruption of maternal care than traditional continuous free-access paradigm, which can have persistent effects on the offspring. The environmental enrichment, a powerful form of experience-dependent plasticity that allows high cognitive, motor and sensory stimulations, is helpful for recovering from different neurological pathologies. Thus, this study aimed at exploring the effects of environmental enrichment on alcohol vulnerability and affective …

Effect of Acetaldehyde Intoxication and Withdrawal on NPY Expression: Focus on Endocannabinoidergic System Involvement

Acetaldehyde (ACD), the first alcohol metabolite, plays a pivotal role in the rewarding, motivational and addictive properties of the parental compound. Many studies have investigated the role of ACD in mediating neurochemical and behavioral effects induced by alcohol administration, but very little is known about the modulation of neuropeptide systems following ACD intoxication and withdrawal. Indeed the neuropeptide Y (NPY) system is altered during alcohol withdrawal in key regions for cerebrocortical excitability and neuroplasticity. The primary goal of this research was to investigate the effects of ACD intoxication and withdrawal by recording rat behavior and by measuring neuropeptide …

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)—or intermittent alcohol drinking paradigm (IAD), along pregestation, gestation, and lactation periods—equivalent to the whole gestational period in humans. Male offspring were reared in standard conditions or EE un…

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, q…

Acetaldehyde self-administration by a two-bottle choice paradigm: Consequences on emotional reactivity, spatial learning, and memory

Abstract Acetaldehyde, the first alcohol metabolite, is responsible for many pharmacological effects that are not clearly distinguishable from those exerted by its parent compound. It alters motor performance, induces reinforced learning and motivated behavior, and produces different reactions according to the route of administration and the relative accumulation in the brain or in the periphery. The effective activity of oral acetaldehyde represents an unresolved field of inquiry that deserves further investigation. Thus, this study explores the acquisition and maintenance of acetaldehyde drinking behavior in adult male rats, employing a two-bottle choice paradigm for water and acetaldehyd…

Benign Prostatic Hyperplasia: Correlations between Receptor Density and Binding Affinity of 1-Adrenoceptors and Several Clinical Parameters

The aim of the study was to determine whether relations do exist between the concentration and activity of 1-adrenoceptors, both inside the prostatic adenoma and the periurethral zone corresponding to the bladder neck, and clinical and biological parameters such as symptoms, evaluated by the American Urological Association (AUA) score, age, weight of the prostate, PSA, and the flow rate. Twenty patients with symptomatic benign prostatic hyperplasia were selected for an open prostatectomy. One gram of tissue was dissected from inside the adenoma and 1 g from the periurethral zone corresponding to the bladder neck. The 1-adrenoceptors were evaluated for the apparent dissociation constant (Kd)…

Upper respiratory tract infections in children: From case history to management

Respiratory tract infections are the most common diseases in childhood. The respiratory tract, widely branched system of ducts, is particularly exposed to the action of microorganisms transmitted by air from here the high frequency of infections they face especially in the first years of life. It is usual distinguish: upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In particular, in infections of the upper airways, the inflammatory process, result of the interaction between microbes and the immune response, can be localized to the mucosa of the nose or sinuses (common cold and sinusitis), or the pharynx or larynx (pharyngotonsillitis and laryngitis) …

Early handling effect on female rat spatial and non-spatial learning and memory

This study aims at providing an insight into early handling procedures on learning and memory performance in adult female rats. Early handling procedures were started on post-natal day 2 until 21, and consisted in 15 min, daily separations of the dams from their litters. Assessment of declarative memory was carried out in the novel-object recognition task; spatial learning, reference- and working memory were evaluated in the Morris water maze (MWM). Our results indicate that early handling induced an enhancement in: (1) declarative memory, in the object recognition task, both at 1h and 24h intervals; (2) reference memory in the probe test and working memory and behavioral flexibility in the…

Dopamine involvement in Acetaldehyde drinking behaviour: role of Ropinirole on.

Rats self-administer acetaldehyde(ACD), ethanol's first metabolite, directly into cerebral ventricles (1), and multiple ICV infusions of ACD produce conditioned place preference (2). ACD, such as alcohol and other substances of abuse, interacts with dopaminergic reward system (3) and its reinforcing and addictive properties have been assessed through an operant-conflict conditioning procedure (4). Since dopamine D2receptor over-expression in the Nacc attenuates alcohol intake (5), this study aims at exploring the effects of ropinirole administration during abstinence, on ACD relapse. The protocol has been scheduled into 3 different periods: training ( animals have been trained to self-admin…

Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex.

Rationale: In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation. Objectives: Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2…

Functional study of GABA-A receptors located on noradrenergic nerve endings in the rat hippocampus following prenatal exposure to diazepam

Psychological assessment in pathological gamblers treated with escitalopram

Pathological Gambling (PG) is classified as a "Disorder of Impulse Control", but due to similarities with drug addiction is frequently described as a drug-free addiction (Potenza et al., 2012). PG is conceptualized as a behavioural addiction because of its neurobiologic, neurophysiologic and psychological features. Current therapeutical approaches seem unsatisfactory as they do not achieve definitive positive outcomes. Considering the well known psycopathological comorbidities, PG represents both a social (impact on relatives money/life) and a sanitary cost, in terms of pharmacological and psychological support. The compulsive behaviour detectable in PG, is a disease with neurophysiopatholo…

Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic–pituitary–adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress respon…

Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats.

Abstract Background Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. Methods As socially stressful events pose particular challenges at developmental stages, this research applied the resident–intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms. Results Binge-like alcohol exposed intruder rats displayed a compromised defensi…

Neuropeptide Y: una overview sugli effetti di neuro- ed immuno-modulazione

Cannabis and the Mesolimbic System

Abstract Cannabis sativa (hemp) is a flowering annual plant whose phytochemical by-products, hashish and marihuana, are the most widely produced and most frequently used illicit drugs in Europe. Δ 9 -Tetrahydrocannabinol is the primary psychoactive constituent, responsible, in a dose-related manner, for euphoria, cognitive effects, and psychotic symptoms, as well as the addictive potential of smoked cannabis due to its interference with the mesolimbic dopaminergic system. Cannabis as well as endocannabinoids acts mainly at the presynaptic levels in several brain regions, including the nucleus accumbens and ventral tegmental area, where it modulates synaptic activity. Through the modulation …

Corrigendum to “Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function”

Effects of a single intense prenatal stress on emotionality and learning performance in adolescent male rat progeny. influence of a daily early short-term maternal separation

Homer2 and alcohol: A mutual interaction

The past two decades of data derived from addicted individuals and preclinical animal models of addiction implicate a role for the excitatory glutamatergic transmission within the mesolimbic structures in alcoholism. The cellular localization of the glutamatergic receptor subtypes, as well as their signaling efficiency and function, are highly dependent upon discrete functional constituents of the postsynaptic density, including the Homer family of scaffolding proteins. The consequences of repeated alcohol administration on the expression of the Homer family proteins demonstrate a crucial and active role, particularly for the expression of Homer2 isoform, in regulating alcohol-induced behav…

D-TMS IN COCAINE ADDICTION: preliminary findings

Cocaine-related disorders are currently among the most devastating mental disease as they leads to profound disturbances in an individual’s behaviour resulting in tremendous economic, social, and moral costs. Imaging studies in human have shown a reduction of dopamine (DA) receptors accompanied by a lesser release of endogenous DA in the ventral striatum (AVT) of cocaine subjects thereby resulting in a ‘dopamine-impoverished’ brain[1-2]. This perturbations lead to neuroadpatations in several other circuits which are related to motivation, inhibitory control, and memory which finally determ compulsive-impulsive self drug administration[3]. The lasting reduction in physiological activity of t…

TRANSCRANICAL MAGNETIC STIMULATION IN COCAINE ADDICTION:PRELIMINARY FINDINGS

Drug addiction is a brain disease which leads to profound disturbances in an individual’s behaviour. In spite of the progress made in the understanding of the neurobiological mechanisms underlying addiction, expectations from a therapeutic point of view have not been satisfying. Given the modest efficacy of therapeutic tools available, Transcranial Magnetic Stimulation (TMS) seems to be a promising “non-pharmacologic” aid in various neuropathologies including addiction which is characterized by a decrease of dopaminergic activity (DA). Thus, ‘restoring’ pre-pathology DA activity may yield clinical benefits in addicts. In particular, it has been reported that TMS reduces the craving for coca…